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Related Concept Videos

M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

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Updated: Jul 4, 2026

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
06:21

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration

Published on: April 27, 2018

Germline CDK12 variants in aggressive prostate cancer.

Sofie H Tolmeijer1, Corinne Maurice-Dror2, Shahneen Sandhu3

  • 1University of British Columbia Vancouver, British Columbia Canada.

Cancer Discovery
|July 2, 2026
PubMed
Summary

Rare germline CDK12 variants drive lethal metastatic prostate cancer (mPCa). These inherited mutations, found in 0.1% of patients, lead to a specific genomic instability signature and are linked to family cancer histories.

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Area of Science:

  • Genetics
  • Oncology
  • Genomic Instability

Background:

  • CDK12 mutations are found in 2-7% of metastatic prostate cancer (mPCa) and were previously thought to be exclusively somatic.
  • Germline variants are rare genetic alterations inherited from parents.

Purpose of the Study:

  • To investigate the role of germline CDK12 truncating variants in metastatic prostate cancer.
  • To determine the frequency and clinical significance of germline CDK12 variants in mPCa.

Main Methods:

  • Screening of 4,535 metastatic prostate cancer patients for germline CDK12 truncating variants.
  • Analysis of tumor genomes for secondary somatic CDK12 variants and genomic instability signatures.
  • Comparison of germline variant frequency with large population control cohorts (gnomAD).
  • Pedigree analysis to confirm germline variant inheritance.

Main Results:

  • Identified five mPCa patients (0.1%) with germline CDK12 truncating variants.
  • All patients exhibited CDK12-driven cancers with a distinct genomic instability signature (tandem duplications).
  • Germline CDK12 variants were significantly enriched in mPCa compared to controls.
  • Family histories and pedigree analyses confirmed inheritance patterns and links to prostate and ovarian cancers.

Conclusions:

  • Germline CDK12 truncating variants are a rare but significant driver of lethal metastatic prostate cancer.
  • These variants contribute to a specific genomic instability phenotype.
  • Germline CDK12 testing may have implications for risk assessment and family cancer counseling.